Non-clinical efficacy

Transcription

1 Non-clinical efficacy 1 st Workshop -Novel Compounds from Renewable Sources David Pereira, Patrícia Valentão, Paula B. Andrade dpereira@ff.up.pt Context The Natural Products Group develops its scientific activities in the chemistry-biology interface. Context 1

2 Context INFLAMMATION CANCER DIABETES NEUROPROTECTION Cell-free - Cell-free - Morphology Morphology Morphology mrna levels mrna levels mrna levels CELL LINES Protein expression Protein expression Protein expression Enzyme activity Enzyme activity Enzyme activity Context A complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. 2

3 The many faces of inflammation Trauma Skin inflammation(e.g. contact dermatitis, fibrosis) Psoriasis Osteoarthritis Liver fibrosis Lung inflammation Delayed type hypersensitivity(dth) Peritonitis Sepsis Acute asthma Chronic asthma Arachidonic acid metabolism n-hydroperoxyeicosatetraenoicacid (HPETs) n-hydroxyeicosatetraenoicacid (HETEs) 3

4 Arachidonic acid metabolism n-hydroperoxyeicosatetraenoicacid (HPETs) n-hydroxyeicosatetraenoicacid (HETEs) Cell lines Anti-inflammatory in anti-inflammatory research research RAW Mouse leukaemic monocyte-macrophage Control LPS 1 µg/ml 4

5 Cell lines Anti-inflammatory in anti-inflammatory research research RAW Control LPS 1 µg/ml Cell Anti-inflammatory lines in anti-inflammatory research research Toll-like receptors vs ROS Nature Immunology 6, (2005) 5

6 Cell Anti-inflammatory lines in anti-inflammatory research research Toll-like receptors vs ROS Control LPS 1 µg/ml Cell Anti-inflammatory lines in anti-inflammatory research research 6

7 Anti-inflammatory research IκB-α NF-κB Pathway p50 p65 IKK P P IκB-α Proteasomal degradation p50 p65 TXA 2 p50 p65 COX-2 inos PGH 2 PGI 2 NO IL-6 PGE 2 TNF-α Cell lines Anti-inflammatory in anti-inflammatory research research DNA RNA Proteins RT-PCR Western Blot inos 130 kd COX-2 72 kd IKB-α 30 kd β-tubulin 55 kd 7

8 Case studies study Cancer Genetic disease, highly regulated Rising incidence& prevalence 2008: 7.8 million deaths. Changes in metabolism& gene expression Treatment: Proliferation Protein kinases Microtubules Angiogenesis APOPTOSIS? Cancer 8

9 Cancer Cancer Cancer 9

10 Cancer Cancer 10

11 Control Ext PA Combination Control Ext PA Combination Cancer Diabetes Diabetes 11

12 Diabetes Diabetes Diabetes α-glucosidase inhibitors α-amylase inhibitors α-amylase Diabetes 12

13 Myrcia spp. 280 nm 350 nm Diabetes Diabetes 13

14 Diabetes 14

15 15

16 Solanum lycopersicum 16

17 SH-SY5Y Human neuroblastoma cell line 17

18 Calls: present & future Funding Calls: present & future FUNDING OPPORTUNITIES DISCOVERY RESEARCH and DEVELOPMENT FET Open research and innovation actions Funding 18

19 Faculdade de Ciências, Universidade do Porto Departamento de Química, Universidade do Minho Faculdade de Ciências e Tecnologias, Universidade do Algarve Tecnologia Farmacêutica, Faculdade de Farmácia da Universidade de Coimbra Laboratório de Farmacognosia, Faculdade de Farmácia da Universidade de Lisboa CSIC, Murcia, Espanha Université de Montpellier, Institut desbiomolécules Max Mousseron IBMM, France Department of Biology, University of Basilicata, Itália Departamento dequímicaanalítica yalimentaria, Facultad de Ciencias, Universidade de Vigo, Espanha Heinrich Heine Universitat, Institute of Pharmaceutical Biology, Dusseldorf, Alemanha 19